Tranexamic acid

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Tranexamic acid
Tranexam.svg
Tranexamic acid ball-and-stick.png
Clinical data
Pronunciation \ˌtran-eks-ˌam-ik-\
Trade names Cyklokapron, others
AHFS/Drugs.com FDA Professional Drug Information
Pregnancy
category
  • B
Routes of
administration
by mouth, injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 34%
Biological half-life 3.1 h
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.013.471
Chemical and physical data
Formula C8H15NO2
Molar mass 157.21 g/mol
3D model (JSmol)
  (verify)

Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss from major trauma, post partum bleeding, surgery, tooth removal, nose bleeds, and heavy menstruation.[1][2] It is also used for hereditary angioedema.[1][3] It is taken either by mouth or injection into a vein.[1]

Side effects are rare.[3] Some include changes in color vision, blood clots and allergic reactions.[3] Greater caution is recommended in people with kidney disease.[4] Tranexamic appears to be safe for use during pregnancy and breastfeeding.[3][5] Tranexamic acid is in the antifibrinolytic family of medications.[4]

Tranexamic acid was discovered in 1962 by Utako Okamoto.[6] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[7] Tranexamic acid is available as a generic medication.[8] The wholesale cost in the developing world is about 4.38 to 4.89 USD for a course of treatment.[9] In the United States a course of treatment costs 100 to 200 USD.[8]

Medical uses[edit]

A one gram vial of TXA

Tranexamic acid is frequently used following major trauma.[10] Tranexamic acid is used to prevent and treat blood loss in a variety of situations, such as dental procedures for hemophiliacs, heavy menstrual bleeding, and surgeries with high risk of blood loss.[11][12]

Trauma[edit]

Tranexamic acid has been found to decrease the risk of death in people who have significant bleeding due to trauma.[13][14] Its main benefit is if taken within the first three hours.[15]

Vaginal bleeding[edit]

Tranexamic acid is used to treat heavy menstrual bleeding.[12] When taken by mouth it both safely and effectively treats regularly occurring heavy menstrual bleeding.[16][17] Another study demonstrated that the dose does not need to be adjusted in females who are between ages 12 and 16.[16]

A 2017 trial found that it decreased the risk of death from bleeding from 1.9% to 1.5% in women with postpartum bleeding.[2] The benefit was greater when the medication was given within three hours.[2]

Surgery[edit]

Dentistry[edit]

In the United States, tranexamic acid is FDA approved for short-term use in people with severe bleeding disorders who are about to have dental surgery.[20] Tranexamic acid is used for a short period of time before and after the surgery to prevent major blood loss and decrease the need for blood transfusions.[21]

Tranexamic acid is used in dentistry in the form of a 5% mouth rinse after extractions or surgery in patients with prolonged bleeding time; e.g., from acquired or inherited disorders.

Other uses[edit]

  • In obstetrics, tranexamic acid is used after delivery to reduce bleeding, often with syntocinon/oxytocin and fundal massage.[citation needed] Since 2010, the WOMAN (World Maternal Antifibrinolytic) trial has been in progress worldwide to establish the efficacy of the drug to arrest postpartum haemorrhage (PPH) in 15 000 women, due to be completed in 2016.[22] Since the drug can be administered orally, it has great potential to reduce maternal mortality rates in developing countries where primary healthcare is often unavailable.[citation needed]
  • In hereditary angioedema[23]
  • In hereditary hemorrhagic telangiectasia - Tranexamic acid has been shown to reduce frequency of epistaxis in patients suffering severe and frequent nosebleed episodes from hereditary hemorrhagic telangiectasia.[24]
  • In melasma - tranexamic acid is sometimes used in skin whitening as a topical agent, injected into a lesion, or taken by mouth, both alone and as an adjunct to laser therapy; as of 2017 its safety seemed reasonable but its efficacy for this purpose was uncertain because there had been no large scale randomized controlled studies nor long term follow-up studies.[25][26]
  • In hyphema - Tranexamic acid has been shown to be effective in reducing risk of secondary hemorrhage outcomes in patients with traumatic hyphema.[27]

Adverse effects[edit]

Common side effects include:[16]

  • Headaches (50.4 – 60.4%)
  • Back aches (20.7 – 31.4%)
  • Nasal sinus problem (25.4%)
  • Abdominal pain (12 – 19.8%)
  • Diarrhea (12.2%)
  • Fatigue (5.2%)
  • Anemia (5.6%)

Rare side effects include:[16]

These rare side effects were reported in post marketing experience and frequencies cannot be determined.[16]

Special populations[edit]

  • Tranexamic acid is categorized as pregnancy category B. No harm has been found in animal studies.[16]
  • Small amounts appears in breast milk if taken during lactation.[16] If it is required for other reasons, breastfeeding may be continued.[28]
  • Tranexamic acid is also not indicated for postmenopausal women and geriatrics.[16]
  • In kidney impairment, tranexamic acid is not well studied. However, due to the fact that it is 95% excreted unchanged in the urine, it should be dose adjusted in patients with renal impairment.[16]
  • In liver impairment, dose change is not needed as only a small amount of the drug is metabolized through the liver.[16]

Mechanism of action[edit]

Tranexamic acid is a synthetic analog of the amino acid lysine. It serves as an antifibrinolytic by reversibly binding four to five lysine receptor sites on plasminogen or plasmin. This prevents plasmin (antiplasmin) from binding to and degrading fibrin and preserves the framework of fibrin's matrix structure.[16] Tranexamic acid has roughly eight times the antifibrinolytic activity of an older analogue, ε-aminocaproic acid.[citation needed]

Society and culture[edit]

TXA was discovered in 1962 by Utako Okamoto.[6] It has been included in the WHO list of essential medicines.[29] TXA is inexpensive and treatment would be considered highly cost effective in high, middle and low income countries.[30]

Brand names[edit]

Tranexamic acid is marketed in the U.S. and Australia in tablet form as Lysteda and in Australia and Jordan it is marketed in an IV form and tablet form as Cyklokapron, in the UK as Cyclo-F and Femstrual, in Asia as Transcam, in Bangladesh as Traxyl, in India as Pause, in South America as Espercil, in Japan as Nicolda, in France and Romania as Exacyl and in Egypt as Kapron. In the Philippines, its capsule form is marketed as Hemostan and In Israel as Hexakapron.[citation needed]

Approval[edit]

The U.S. Food and Drug Administration (FDA) approved tranexamic acid oral tablets (brand name Lysteda) for treatment of heavy menstrual bleeding on 13 November 2009.[citation needed]

In March 2011 the status of tranexamic acid for treatment of heavy menstrual bleeding was changed in the UK, from PoM (Prescription only Medicines) to P (Pharmacy Medicines)[31] and became available over the counter in UK pharmacies under the brand names of Cyklo-F and Femstrual, initially exclusively for Boots pharmacy, which has sparked some discussion about availability.[32] (In parts of Europe it had then been available OTC for over a decade.[citation needed]) Regular liver function tests are recommended when using tranexamic acid over a long period of time.[33]

References[edit]

  1. ^ a b c British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 170. ISBN 9780857111562. 
  2. ^ a b c Shakur, Haleema; Roberts, Ian; Fawole, Bukola (April 2017). "Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial". The Lancet. doi:10.1016/S0140-6736(17)30638-4. 
  3. ^ a b c d "Cyklokapron Tablets - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. September 2016. Archived from the original on 20 December 2016. Retrieved 14 December 2016. 
  4. ^ a b "Tranexamic Acid Injection - FDA prescribing information, side effects and uses". www.drugs.com. Archived from the original on 21 December 2016. Retrieved 14 December 2016. 
  5. ^ "Tranexamic acid Use During Pregnancy | Drugs.com". www.drugs.com. Archived from the original on 21 December 2016. Retrieved 14 December 2016. 
  6. ^ a b Geoff Watts (2016). "Obituary Utako Okamoto". The Lancet. 387 (10035): 2286. doi:10.1016/S0140-6736(16)30697-3. 
  7. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016. 
  8. ^ a b Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. X. ISBN 9781284057560. 
  9. ^ "Tranexamic Acid". International Drug Price Indicator Guide. Retrieved 8 December 2016. 
  10. ^ Binz, S; McCollester, J; Thomas, S; Miller, J; Pohlman, T; Waxman, D; Shariff, F; Tracy, R; Walsh, M (2015). "CRASH-2 Study of Tranexamic Acid to Treat Bleeding in Trauma Patients: A Controversy Fueled by Science and Social Media". Journal of blood transfusion. 2015: 874920. doi:10.1155/2015/874920. PMC 4576020Freely accessible. PMID 26448897. 
  11. ^ Melvin, JS; Stryker, LS; Sierra, RJ (22 October 2015). "Tranexamic Acid in Hip and Knee Arthroplasty". The Journal of the American Academy of Orthopaedic Surgeons. 23: 732–40. doi:10.5435/JAAOS-D-14-00223. PMID 26493971. 
  12. ^ a b Tengborn, L; Blombäck, M; Berntorp, E (February 2015). "Tranexamic acid--an old drug still going strong and making a revival". Thrombosis research. 135 (2): 231–42. doi:10.1016/j.thromres.2014.11.012. PMID 25559460. 
  13. ^ Cherkas, David (Nov 2011). "Traumatic Hemorrhagic Shock: Advances In Fluid Management". Emergency Medicine Practice. 13 (11). Archived from the original on 18 January 2012. 
  14. ^ "Drug will save lives of accident victims, says study". BBC News. 2010. Archived from the original on 24 June 2010. Retrieved 3 June 2016. 
  15. ^ Napolitano, Lena M.; Cohen, Mitchell J.; Cotton, Bryan A.; Schreiber, Martin A.; Moore, Ernest E. (2013). "Tranexamic acid in trauma". Journal of Trauma and Acute Care Surgery. 74 (6): 1575–86. doi:10.1097/TA.0b013e318292cc54. PMID 23694890. 
  16. ^ a b c d e f g h i j k "Lysteda (tranexamic acid) Package Insert" (PDF). accessdata.FDA.gov. Archived (PDF) from the original on 4 March 2016. Retrieved 2 November 2015. 
  17. ^ Lukes, AS; Moore, KA; Muse, KN (2010). "Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial". Obstet Gynecol. 116 (4): 865–875. doi:10.1097/AOG.0b013e3181f20177. PMID 20859150. 
  18. ^ RCPCH. "Evidence Statement Major trauma and the use of tranexamic acid in children Nov 2012" (PDF). Retrieved 17 December 2012. 
  19. ^ Sethna, N. F.; Zurakowski, D; Brustowicz, R. M.; Bacsik, J; Sullivan, L. J.; Shapiro, F (2005). "Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery". Anesthesiology. 102 (4): 727–32. doi:10.1097/00000542-200504000-00006. PMID 15791100. 
  20. ^ "Cyklokapron (tranexamic acid) Product Information" (PDF). Archived (PDF) from the original on 29 February 2016. Retrieved 3 November 2015. 
  21. ^ Forbes CD, Barr RD, Reid G; et al. (1972). "Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease". Br Med J. 2 (5809): 311–313. doi:10.1136/bmj.2.5809.311. 
  22. ^ "Protocol 09PRT/4179:Tranexamic acid for the treatment of postpartum haemorrhage: an international, randomised, double blind, placebo controlled trial (the WOMAN Trial)". The Lancet. Elsevier Limited. n.d. Retrieved 3 June 2016. 
  23. ^ Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-06911-5. [page needed]
  24. ^ Klepfish, A; Berrebi, A; Schattner, A (2001). "Intranasal tranexamic acid treatment for severe epistaxis in hereditary hemorrhagic telangiectasia". Archives of Internal Medicine. 161 (5): 767. doi:10.1001/archinte.161.5.767. PMID 11231712. 
  25. ^ Zhou, LL; Baibergenova, A (27 February 2017). "Melasma: systematic review of the systemic treatments". International Journal of Dermatology. doi:10.1111/ijd.13578. PMID 28239840. 
  26. ^ Taraz, M; Niknam, S; Ehsani, AH (30 January 2017). "Tranexamic acid in treatment of melasma: A comprehensive review of clinical studies". Dermatologic therapy: e12465. doi:10.1111/dth.12465. PMID 28133910. 
  27. ^ Gharaibeh, Almutez; Savage, Howard I.; Scherer, Roberta W.; Goldberg, Morton F.; Lindsley, Kristina (2013-12-03). "Medical interventions for traumatic hyphema". The Cochrane Database of Systematic Reviews (12): CD005431. doi:10.1002/14651858.CD005431.pub3. ISSN 1469-493X. PMC 4268787Freely accessible. PMID 24302299. 
  28. ^ "Tranexamic Acid use while Breastfeeding". www.drugs.com. 7 November 2014. Archived from the original on 18 September 2016. Retrieved 27 May 2016. 
  29. ^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Archived (PDF) from the original on 13 May 2015. Retrieved 10 May 2015. 
  30. ^ Guerriero, Carla; Cairns, John; Perel, Pablo; Shakur, Haleema; Roberts, Ian; Crash 2 Trial, Collaborators (2011). "Cost-Effectiveness Analysis of Administering Tranexamic Acid to Bleeding Trauma Patients Using Evidence from the CRASH-2 Trial". PLoS ONE. 6 (5): e18987. Bibcode:2011PLoSO...618987G. doi:10.1371/journal.pone.0018987. PMC 3086904Freely accessible. PMID 21559279. 
  31. ^ Tranexamic Acid to be available OtC Archived 9 October 2011 at the Wayback Machine.[full citation needed]
  32. ^ In defence of multiple pharmacies Archived 28 March 2012 at the Wayback Machine.[full citation needed]
  33. ^ Allen, Helen (13 June 2012). "Tranexamic acid for bleeding". Patient UK. Archived from the original on 25 May 2014. 

External links[edit]